FDA Issues Clarification on Sildenafil Use in Children with PAH

Apr 14, 2014

ACC News Story

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The U.S. Food and Drug Administration (FDA) is clarifying its previous recommendation related to prescribing sildenafil (Revatio) for children with pulmonary arterial hypertension (PAH). Sildenafil is FDA-approved only to treat PAH in adults, not in children; however, the FDA says health care professionals must consider whether the benefits of treatment with the drug are likely to outweigh its potential risks for each patient.

"The Adult Congenital and Pediatric Cardiology community would like to thank the FDA for issuing this important clarification related to the intent of its prior warning," said Kathy J. Jenkins, MD, MPH, FACC, chair of the ACC's Adult Congenital and Pediatric Cardiology Council. "Children with pulmonary hypertension and certain related conditions have limited available treatments, and sildenafil at lower doses is an important option. This clarification should remove any barriers to prescribing the drug in the right circumstances."

FDA revised the sildenafil drug label in August 2012, adding a warning stating that "use of [sildenafil], particularly chronic use, is not recommended in children." This recommendation was based on an observation of increasing mortality with increasing sildenafil doses in a long-term clinical trial in pediatric patients with PAH. FDA also issued a Drug Safety Communication at that time.

According to the FDA, the purpose of the recommendation was to raise awareness of clinical trial results showing a higher risk of mortality in pediatric patients taking a high dose of sildenafil when compared to pediatric patients taking a low dose. However, the agency says the recommendation was not intended to suggest that sildenafil should never be used in children.

"This issue highlights the important problem of the limited studies of drugs for rare pediatric diseases compared to adults," Jenkins noted. “Pediatric cardiologists must extrapolate from many sources of information, as published studies are few, in order to devise the best strategies for children."

The ACC, along with the American Academy of Pediatrics and the American Heart Association, had raised concerns directly with the FDA about the initial recommendation. In a letter from October 2013, the organizations noted, among other reasons, that the European Medicines Agency (EMA) approved sildenafil therapy for use in children with PAH after reviewing the same data the FDA reviewed; and that there are limited treatment options for PAH in children. "In some cases, the FDA warning has resulted in loss of insurance coverage of sildenafil," the letter notes. "Withdrawal of treatment can prove fatal in patients with severe disease. Replacement with continuous intravenous prostacyclin therapy is associated with significant additional risks."

In a statement announcing the clarification, the FDA said: "The evidence behind our initial recommendation has not changed; we are simply clarifying the strength of the warning communicated in the [sildenafil] drug label." "We recognize there may be situations in which the benefit-risk profile of [sildenafi] may be acceptable in individual children, for example, when other treatment options are limited and [sildenafil] can be used with close monitoring."